Somatic Mutations in the BRAF, KRAS, NRAS, EIF1AX, and TERT Genes: Diagnostic Value in Thyroid Neoplasms.

The feasibility of using molecular genetic markers associated with thyroid neoplasms and more aggressive course of the disease is now actively studied. We analyzed the diagnostic value of somatic mutations in the hot spots of BRAF, KRAS, KRAS, EIF1AX, and TERT genes in histological material from 153 patients with thyroid gland neoplasms. BRAF mutations (exon 15, codon area 600-601) were found in 54 patients, NRAS mutations (exon 3, codon 61) were detected in 12 patients; mutations KRAS, TERT, and EIF1AX genes were not detected.

[Prediction of surgical treatment for differentiated thyroid carcinoma].

The purpose of the study was to determine the influence of various factors on the prediction of surgical treatment for differentiated thyroid carcinoma (TC). The long-term results of surgical treatment were studied in 266 patients with differentiated forms of TC who had been operated on at the Surgical Department of the Endocrinology Research Center in 2000-2003. To solve the put problem, the authors identified the following factors that may influence the prediction of surgical treatment for differentiated TC forms, as shown by the data available in the literature; these included gender, age, the morphological characteristics and size of a tumor, the scope and procedure of surgical intervention, the presence of metastases, postoperative radioactive iodine therapy, and suppressive levolhyroxine therapy. The investigation established the most important/actors significantly influencing the prediction of surgical treatment for differentiated TC forms. It showed the high probability of metastases being in the cervical VI lymph nodes unchanged, as evidenced by preoperative ultrasound study. The optimal algorithm was developed for the treatment of patients with differentiated TC forms - thyroidectomy, by removing fat and lymph nodes of the VI-level neck in combination with radioactive iodine therapy and suppressive L-T4 therapy.

[Sclerotherapy in patients with nodular colloid goiter].

Results of percutaneous sclerotherapy with ethanol (PSTE) in 89 patients with nodular colloid goiter were analyzed. Indications and method of PSTE in different types of nodular formations were determined. All the patients were divided into 3 groups: 1st group -- 8 (9%) patients with free-functioning nodes, 2nd -- 16 (18%) patients with symptoms of cervical organs compression, 3rd -- 65 (73%) patients with cosmetic defect on neck. It is concluded that PSTE may be regarded as alternative for surgical treatment in the patients with high surgical risk. It is not pathogenic method of treatment and it should be accompanied with medicament therapy of iodine-deficient goiter. Liquidation of clinical symptoms is the criterion of treatment efficiency.

[Thyroid cancer].

The prevalence of nodular lesions of the thyroid gland (thyroid gland), according to various researchers, ranges from 3 to 7%]. The widespread introduction of ultrasound (ultrasound) in clinical practice, as well as the results of autopsy studies, showed that the prevalence of nodular lesions of the thyroid gland is much higher and is about 50%, especially at the age of over 50. In women, thyroid nodes are detected 2-4 times more often than in men. Children suffer from nodular lesions extremely rarely. The incidence of nodular goiter is directly proportional to age. The increase in the incidence of nodular goiter is approximately 0.1% per year at a young age and gradually reaches 2%. The prevalence of thyroid cancer (thyroid cancer) among nodular goiter, according to various authors, is from 1 to 6%. It should be noted that the prevalence in the population of nodular goiter is so high both in the regions of iodine deficiency and with normal iodine supply, but in the first case it is slightly higher. The incidence of thyroid cancer in absolute terms does not depend on the level of iodine supply. Thus, in a situation of a slightly higher incidence of banal nodular colloid goiter in the regions of iodine deficiency, the proportion of cancer among all cases of nodular goiter will be less. It is important to note that these data make it possible to equally use the results of studies on thyroid cancer obtained in regions with different iodine supply.

[Clinical guidelines developed by the Russian Association of Endocrinologists for the diagnosis and treatment of nodular goiter].

The guidelines presented do not pretend to be a systematic presentation of all aspects of the diagnosis and treatment of nodular goiter and are not intended to replace guidelines for various medical disciplines. In real clinical practice, situations may arise that are beyond the scope of the recommendations presented, in connection with which the final decision regarding a specific patient and responsibility for him lies with the attending physician.The recommendations presented are mainly devoted to the diagnosis and treatment of nodular (multinodular) euthyroid colloid, differently proliferating goiter in adults (over 18 years of age) and are the agreed opinion of the RAE experts who developed them. Nodular (multinodular) toxic goiter, tumors (malignant and benign), as well as other diseases that can manifest themselves by nodular formations of the thyroid gland (thyroid gland), are discussed mainly in the context of differential diagnosis. The recommendations also do not affect the features of diagnosis and treatment of nodular goiter in children and adolescents.

[Target thin-needle puncture biopsy in diagnosis of thyroid cancer]. / Pritsel'naia tonkoigol'naia punktsionnaia biopsiia v diagnostike raka shchitovdnoi zhelezy.

One hundred medical histories of patients with thyroid cancer (TC) were analyzed. Patients were divided into two groups depending on the variant of thin-needle biopsy technique (TNB). In group 1TNB was performed with "blind" method (with palpation control)--43 cases, in group 2 target TNB (ultrasound-guided) was carried out--57 cases. Patients of each group were divided depending on cytological presurgical diagnosis. Statistical analysis was carried out with two-sided Fisher's criterion. It is demonstrated that detection of TC in group 2 (84.2%) was higher than in group 1 (62.8%) where "blind" method of puncture was used (p = 0.020). It is recommended to perform target TNB in all cases of nodular goiter that improves quality of TC diagnosis.

[Analysis of mutations in the RET proto-oncogene in patients with medullary thyroid tumor]. / Analiz mutatsii v protoonkogene RET u bol'nykh s medulliarnym rakom shchitovidnoi zhelezy.

The spectrum of mutations of the RET protooncogene was analyzed in Russian patients with inherited or sporadic medullary thyroid carcinoma (MTC). Four RET exons (11, 13, 15, and 16) were subjected to molecular analysis, and mutations were revealed and identified in 47.4% (9/19) patients with sporadic MTC. In total, six mutations (including three new ones) were observed. The most common mutation affected codon 918 to cause substitution of methionine with threonine and accounted for 31.6% alleles. Analysis of exons 11 and 16 revealed four mutations in patients with inherited multiple endocrine neoplasia type 2 (MEN 2). Mutations were found in each patient. Thyroidectomy was performed in four asymptomatic carriers of RET mutations from three MET 2A families (in two families, affected relatives had bilateral pheochromocytoma). In two patients, analysis of the surgery material revealed MTC microfoci in both lobes of the thyroid gland. The results provide the ground for constructing a bank of genetic information on Russian MTC patients with the clinically verified diagnosis.

[Long-term results of the surgical treatment of patients with multinodular euthyroid goiter]. / Otdalennye rezul'taty khirurgicheskogo lecheniia bol'nykh mnogouzlovym éutireoidnym zobom.

Long-term results of treatment of 280 patients operated for multinodal euthyroid goiter (MNEG) in surgical department of Endocrinology Research Center RAMS from 1983 to 1997 were studied. Hormonal examination of peripheral blood, ultrasonic examination of thyroid gland (TG) and zones of regional lymph outflow, thin-needle punch biopsy were used as special methods of investigation. Correlation between recurrence and histological form was studied. In cystic-colloid goiter with adenomatosis the recurrence of MNEG was revealed in 15 (34.1%) cases. In primary multiple TG adenomas of different types the number of recurrences was smallest--1 (3.3%) cases. There were no recurrences in cancer of TG in combination with cystic-colloid goiter or adenomas of TG. Recurrence of cystic-colloid goiter was revealed in 5 (5.7%) cases, different types of adenomas--in 5 (5.7%) cases. The smallest number of recurrences of MNEG was seen after maximum subtotal resection of TG--in 4 patients (7.7% of the patients with this volume of operation). In all the 12 cases of partial resection of TG the recurrence of different morphological forms of MNEG was revealed. Influence of thyroid therapy on remote recurrence rate in different form of MNEG was also studied. In cystic-colloid goiter (CCG) of different proliferation degree with adenomatosis the recurrence rate was not significantly different irrespective of hormonal therapy--29.4%, 37.5% and 36.4%, respectively, in adequate therapy, inadequate therapy and its absence, that testifies to small influence of thyroid therapy on reduction of recurrence rate in this group of patients. The highest recurrence rate in CCG and CCG with adenomas of TG was revealed in the group without thyroid therapy--30.8% and 35.7%, respectively.

[Thin-needle aspiration biopsy of solitary formations of the thyroid gland]. / Tonkoigol'naia aspiratsionnaia biopsiia solitarnykh obrazovanii shchitovidnoi zhelezy.

The paper analyzes the use of thin-needle aspiration biopsy in 372 patients with thyroid solitary formations. By the results of clinical and instrumental studies and cytological examination of thyroid puncture specimens groups of patients with individual clinical and morphological types of the disease were identified. Differential surgical policy in each group of patients was shown on the basis of the finding. It is concluded that thin-needle aspiration biopsy should be integrated into the compulsory programme of comprehensive examination of patients with thyroid solitary formations. Having a high efficiency, the above method helps in most cases to make an accurate clinical and morphological diagnosis and to choose the optimal treatment policy for each specific patient admitted to a surgical hospital for an aggregate diagnosis of nodal euthyroid goiter. Some patients may avoid unjustifiable surgical intervention and be on conservative therapy under follow-up.

[Plasmapheresis in combined treatment of severe generalized myasthenia]. / Plazmaferez v kompleksnom lechenii tiazheloi generalizovannoi miastenii.

Experience in the application of plasmapheresis in various stages of treatment is analysed. It was conducted in 52 patients with severe forms of generalized myasthenia; 12 of them were males and 40 were females. It is noted that plasmapheresis is very effective in the preoperative period for the preparation of patients for operation and is ineffective in medicamentous therapy. In the late-term periods after thymectomy plasmapheresis is mainly recommended for arresting crises and precritical conditions because of the rapid and short effect of the method. In patients who underwent thymectomy and splenectomy the effect of plasmapheresis in the late-term period after the operation was of a longer duration. Research must be continued and clinical experience accumulated to identify exactly the mechanism of the effect of plasmapheresis on the myasthenic status and the immune and neuroendocrine systems and to determine the place of the method in the complex of therapeutic measures.